Myelin, Movement, and the Mind:

Hot Topics in MS Research

April 12, 2016

Presented by:

Teva Pharmaceuticals | Acorda Therapeutics

Mallinckrodt Pharmaceuticals Autoimmune and Rare Diseases, US Bank

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Myelin, Movement, and the Mind:

Hot Topics in MS Research

April 12, 2016

Presented by:

Teva Pharmaceuticals | Acorda Therapeutics

Mallinckrodt Pharmaceuticals Autoimmune and Rare Diseases, US Bank

John Schafer, MD

Director of Mercy MS Center and Mercy Achievement Center

Sacramento, CA

Meghan Beier, PhD

Johns Hopkins University School of Medicine

Baltimore, MD

Abbey J. Hughes, PhD

Assistant Professor, Department of Rehabilitation Medicine

University of Washington School of Medicine

Seattle, WA

Agenda

• Myelin Repair and new developments in stem cell research ~ John Schaefer, MD

• Movement, Reasons to Stay Active When You Have Multiple Sclerosis~ Meghan Beier, PhD

• Mindfulness and Meditation Treatment Options ~ Abbey Hughes, PhD

Myelin Repair and Stem Cells

John Schafer, MD

Myelin

Myelin

Myelin

Myelin

•Symptoms in MS are caused by damage to myelin or nerve cells (axons) in the brain, spinal cord and optic nerves.

•This damage to the myelin and axons is caused by certain types of cells and activities in the immune system

Myelin

15

Inflammation//demyelination Nerve cell loss

Course of MS

•Can putting myelin back on demyelinated nerves and/or creating new nerve cells restore function that is lost in multiple sclerosis?

Fixing broken nerve cells

•Anti-Lingo antibody •Slows down the molecule that puts the brakes on myelin production.

•Is currently in trials (RENEW Trial in optic neuritis)

•Remyelinating antibody (M. Rodriguez)

•Drugs which encourage myelin growth.

Remyelination

•Stem cells are cells which have not yet become specialized and have the potential for developing into any type of cell in the body.

Stem Cells and MS

•Replace the immune system

•Repair the damaged nervous system

How stem cells could help MS

The Immune System and MS

•Replace the current immune system, which is causing damage to myelin and nerve cells with a new immune system which would not cause damage.

•How to replace the immune system: •Destroy the current immune system with radiation and chemotherapy.

• Introduce hematopoietic stem cells which would then build a new immune system.

Stem Cells and MS

•Problems with immune ablation and hematopoetic stem cell replacement.

•Side effects may be considerable

•Won’t necessarily fix damage that has already been done.

•Benefits and risks must be compared to those of the MS drugs which have multiplied during the same period of time as the stem cell techniques have been developed.

Stem Cells and MS

•Stem cells to repair the damaged nervous system.

• Replace oligodendroglia to make more myelin

• Replace damaged nerve cells

• Replace cells that nourish and protect nerve cells and myelin

Stem Cells and MS

Stem Cells and MS -Questions

•Where to get the stem cells? •Mesenchymal stem cells

•Embryonic stem cells

•Neural stem cells / oligodendrocyte precursor cells

•Induced pluripotent stem cells

•Where to put the stem cells?•Into the brain, blood stream or spinal fluid?

•How to get the stem cells to develop into the cells necessary to do the job?

•Stem cell science is exciting and may bring new options for treatment.

• Immune ablation and reconstitution is in clinical trials at a few prominent medical centers.

•Stem cell replacement of injured cells is still a long way off. Experts doing this research warn that it should be done only in clinical trials.

Stem Cells

Meghan Beier, PhD

Movement, Reasons to Stay

Active When You Have

Multiple Sclerosis

Special Thanks to Kathy Zackowski, PhD, OTR who shared slides and resources

Movement, Reasons to Stay Active When You Have Multiple Sclerosis

“Regular physical activity is one of the most important things you can do for your health.”

~ Centers for Disease Control and Prevention (CDC)

“The single thing that comes close to a magic bullet, in terms of its strong and

universal benefits, is exercise.” ~ Frank Hu, Epidemiologist, Harvard School of Public Health, Harvard Magazine

2007

Special Thanks to Kathy Zackowski, PhD, OTR who shared slides and resources

Sedentary behavior may lead to negative health outcomes for

persons with MS, such as:

•Cardiovascular Disease

•Reduced Mobility

•Cognitive dysfunction• Up to 65%3

•Pain – chronic and acute

• 50 – 65%1

•Fatigue• 50 – over 90%2, 3

•Anxiety, worry•14 – 40%4

•Difficulties with sleep• 50%2

•Depression• Up to 60%3

•Sexual dysfunction•67 – 75%5

1. Ehde, Osborne, Hanley, Jensen, & Kraft, 2006; Hadjimichael, Kerns, Rizzo, Cutter, & Vollmer, 2007; Khan &

Pallant, 2007

2. Induruwa, Constantinescu, Gran, 2012

3. Chiaravalloti & DeLuca, 2008

4. Hartoonian, Terrill, Beier, Turner, Day, Alschuler, under review

5. Foley, Zemon, Campagnolo, Devitt, Tyry, Marrie, Cutter, Sipski, Vollmer, 2007; Valleroy & Kraft, 1984

Prevalence of Common Symptoms

•Improved quality of life

•Weight loss

•Stronger bones and

muscles

•Reduced risk of:•Cardiovascular disease, such as

heart disease or stroke

•Type 2 diabetes

•Metabolic syndrome

•Cancer; specifically colon,

breast, endometrial, and lung

cancers

•Falls

•Improved mood

•Better sleep

•More energy, less fatigue

•Improved sexual

functioning •increased arousal in women

•fewer problems with erectile

dysfunction in men

•Improved cognition

•executive functioning

•Longer life

Benefits of Exercise

•Improved quality of life

•Weight loss

•Stronger bones and

muscles

•Reduced risk of:•Cardiovascular disease, such as

heart disease or stroke

•Type 2 diabetes

•Metabolic syndrome

•Cancer; specifically colon,

breast, endometrial, and lung

cancers

•Falls

•Improved mood

•Better sleep

•More energy, less fatigue

•Improved sexual

functioning •increased arousal in women

•fewer problems with erectile

dysfunction in men

•Improved cognition

•executive functioning

•Longer life

Benefits of Exercise

Strength, Walking, and Reduced Falls

85% of people with MS report reduced mobility as a major limitation

•A 2013 review of 54 studies found moderate exercise two times per week

improved aerobic capacity, and increased muscle strength

•Walking improved by 19%; 32% if training was supervised

Greater than 50% of people with MS fall

Fall rates range from 1.6 to 18.4 falls per individual, per year

•All exercise interventions helped

•Those focused on balance and strength seemed to work best

Sosnoff, J. J., & Sung, J. (2015). Reducing falls and improving mobility in multiple sclerosis. Expert Review of Neurotherapeutics, 15(6), 655–666.

•Improved quality of life

•Weight loss

•Stronger bones and

muscles

•Reduced risk of:•Cardiovascular disease, such as

heart disease or stroke

•Type 2 diabetes

•Metabolic syndrome

•Cancer; specifically colon,

breast, endometrial, and lung

cancers

•Falls

•Improved mood

•Better sleep

•More energy, less fatigue

•Improved sexual

functioning •increased arousal in women

•fewer problems with erectile

dysfunction in men

•Improved cognition

•executive functioning

•Longer life

Benefits of Exercise

Exercise, Mood, and Multiple Sclerosis

Depression: Up to 50%

•20 minutes of walking or yoga,

immediate improvement in mood

•Progressive strength training:

improved depression after 12

weeks

•Aerobic exercise: 40min, 3 times

per week reduced depression

Anxiety, Worry: 14 to 40%

• Not much research in MS

• Among patients with chronic

illness, any exercise reduced

anxiety

• Greatest reduction seen for 12

week programs, duration at least

30 minutes

Effects of Single Bouts of Walking Exercise and Yoga on Acute Mood Symptoms in People with Multiple Sclerosis., 18(1), 1–8.

Pedersen, B. K., & Saltin, B. (2015). Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scandinavian Journal of Medicine & Science in Sports,

25 Suppl 3, 1–72.

Herring, M. P., & O'Connor, P. J. (2010). The effect of exercise training on anxiety symptoms among patients: a systematic review. Archives of Internal Medicine

•Improved quality of life

•Weight loss

•Stronger bones and

muscles

•Reduced risk of:•Cardiovascular disease, such as

heart disease or stroke

•Type 2 diabetes

•Metabolic syndrome

•Cancer; specifically colon,

breast, endometrial, and lung

cancers

•Falls

•Improved mood

•Better sleep

•More energy, less fatigue

•Improved sexual

functioning •increased arousal in women

•fewer problems with erectile

dysfunction in men

•Improved cognition

•executive functioning

•Longer life

Benefits of Exercise

(Skjerbæk et.al, Multiple Sclerosis, 2012)Slide provided by Dr. Zackowski

Exercise Options: Physical Therapy

•Can improve:

•walking speed

•endurance

•balance

•gait

•Moo

•Try to walk for 20 minutes or more

•If you use a treadmill, try walking

with an uphill or downhill grade,

which may help improve balance

and gait

Exercise Options: Walking

www.abovems.com

www.mssociety.org.uk

www.sitandbefit.org

www.nchpad.org

Exercise Options: Home Exercise

Each National MS Society

Chapter keeps a listing of

professionals that have taken

the NMSS training for fitness

professionals.

Exercise Options: Finding an Expert or Classes

Exercise Options: Aquatic Exercises

Exercise Options: Cycling

Mindfulness in MS

•Overview of today’s topics•What is mindfulness?

•What are some of the benefits of mindfulness for people with MS?

•Mindfulness-based treatments •Mindfulness-based stress reduction

•Mindfulness-based cognitive therapy

•Mindful movement

•Two introductory mindfulness exercises•Mindful breathing

•Progressive muscle relaxation

What is Mindfulness?

•History1

• Ancient Hindu (1500 BCE), Dao (600 BCE) and Buddhist (535 BCE) practices

• Also found in Christian, Jewish, and Muslim practices

• Focus on breathing, calmness, presence of mind

•1970s• Applied to clinical psychology and psychiatry

practices• Jon Kabat-Zinn (1979) founded Mindfulness-Based

Stress Reduction (MBSR)2

What is Mindfulness?

•Definitions2

•“Paying attention in a particular way: on purpose, in the present moment, and nonjudgmentally”

•“Bringing one’s attention to the present experience on a moment-to-moment basis”

•“Moment-by-moment awareness”

•“Gentle effort to be continuously present with experience.”

What is Mindfulness?

•Two components3

•Self-regulation of attention, focused on the present experience

•Emphasis on observation

•Approaching the present moment with curiosity, openness, and acceptance

•Emphasis on allowing the mind to wander rather than controlling it in a particular state

Benefits of Mindfulnessin MS

•Physical health benefits4

•Improvements in standing balance5

•Reductions in bodily pain6

•Reductions in fatigue6,7

•Mental health benefits4

•Reductions in anxiety5,7

•Reductions in depression5,7

•Quality of life benefits4

•Improvements in well-being7

•Improvements in health-related quality of life7

Mindfulness-based Treatments

•Mindfulness-based Stress Reduction (MBSR)7

•Most well-studied

•Typically conducted in group sessions (4-12 weeks), can also be individual sessions

•Applied in many chronic health populations, (e.g., chronic pain, depression, anxiety, stroke, HIV)

•3 meditation strategies:•awareness of breath

•awareness of body

•mindful movement

Mindfulness-based Treatments

•Mindfulness-based Cognitive Therapy (MBCT)9

•Based on MBSR

•Employs cognitive therapy strategies, based on Aaron Beck’s Cognitive Therapy of Depression10

•Identify unhelpful/maladaptive patterns of thinking and behavior

•Changing (“restructuring”) unhelpful thought patterns results in improvements in emotions and behavior

•Uses mindfulness strategies to prevent relapse of depression or mood disorders

Mindfulness-based Treatments

•Mindful Movement5,11

•A variety of practices:•Tai Chi – focuses on martial art

•Qi Gong – focuses on movement to guide energy

•Yoga – focused on spiritual, mental, and physical practice

•Reduces stress

•Enhances strength and flexibility

•Improves mood, concentration, relaxation

Practice Exercise 1:Mindful Breathing

•Get into a comfortable sitting or reclined position•Loosen any tight clothing

•Uncross legs

•Place one hand on chest, one hand on abdomen

•Take three deep, relaxed breaths, counting to 3 for each inhale, and 3 for each exhale

•Focus on allowing your abdomen to rise and fall, while keeping your chest still

•Continue for 2-10 minutes

Practice Exercise 1: Progressive Muscle Relaxation

•Get into a comfortable sitting or reclined position

•Begin with mindful breathing for 1-2 minutes

•Start at your feet and work your way up, focusing on one muscle group at a time

•Curl your toes downward, hold for 5 sec, relax

•Flex your feet upward, hold for 5s, relax•Flex your thigh muscles, hold for 5s, relax

•Flex your buttocks, hold for 5s, relax

•Arch your back, hold for 5s, relax•Tighten your abdominal muscles, hold for 5s, relax

•Push out your chest, hold for 5s, relax

•Clench your fists, hold for 5s, relax•Flex your biceps, hold for 5s, relax

•Raise your shoulders, hold for 5s, relax

•Gently roll your neck forward, hold for 5s, relax•Gently roll neck backward, hold for 5s, relax

•Smile as wide as you can, hold for 5s, relax

•Close your eyes tightly, hold for 5s, relax•Raise your eyebrows, hold for 5s, relax

References

1. Sujato, B. (2012). A history of mindfulness. Taiwan: Santipada.

2. Kabat-Zinn, J. (1994). Wherever you go, there you are: Mindfulness meditation in everyday life.

3. Bishop, S. R., Lau, M., Shapiro, S., Carlson, L., Anderson, N. D., Carmody, J., . . . Devins, G. (2004).

Mindfulness: A proposed operational definition. Clinical psychology: Science and practice, 11(3): 230-241.

4. Simpson, R., Booth, J., Lawrence, M., Byrne, S., Mair, F., & Mercer, S. (2014). Mindfulness based

interventions in multiple sclerosis-a systematic review. BMC neurology, 14(1), 1.

5. Mills, N., & Allen, J. (2000). Mindfulness of movement as a coping strategy in multiple sclerosis: a pilot

study. General hospital psychiatry, 22(6), 425-431.

6. Tavee, J., Rensel, M., Planchon, S. M., Butler, R. S., & Stone, L. (2011). Effects of meditation on pain and

quality of life in multiple sclerosis and peripheral neuropathy: A pilot study. International journal of MS

care, 13(4), 163-168.

7. Grossman, P., Kappos, L., Gensicke, H., D'souza, M., Mohr, D. C., Penner, I. K., & Steiner, C. (2010). MS

quality of life, depression, and fatigue improve after mindfulness training A randomized

trial. Neurology, 75(13), 1141-1149.

8. Grossman, P., Niemann, L., Schmidt, S., & Walach, H. (2004). Mindfulness-based stress reduction and

health benefits: A meta-analysis. Journal of psychosomatic research, 57(1), 35-43.

9. Teasdale, J. D., Segal, Z. V., Williams, J. M. G., Ridgeway, V. A., Soulsby, J. M., & Lau, M. A. (2000).

Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. Journal of

consulting and clinical psychology, 68(4), 615.

10. Beck, A. T., Rush, A. J., Shaw, B. F., & Emery, G. (1987). Cognitive therapy of depression. New York:

Guilford Press.

11. Khalsa, S.B. (2004). Yoga as a therapeutic intervention: A bibliometric analysis of published research

studies. Indian J Physiol Pharmacol, 48(3), 269-285.

Thank You!

John Schafer, MD Meghan Beier, PhD Abbey J. Hughes, PhD

Questions/Comments

Can Do MS Resources

Find these resources at www.MSCanDo.org.

National MS Society Resources

nationalMSsociety.org

Mind and Body: A Winning Team

in Stress Management

May 10, 2016

Presented by:

Teva Pharmaceuticals | Acorda Therapeutics

Mallinckrodt Pharmaceuticals Autoimmune and Rare Diseases | US Bank